A host of data on genetic variation from the Human Genome and International HapMap projects, and advances in high-throughput genotyping technologies, have made genome-wide association (GWA) studies technically feasible. GWA studies help in the discovery and quantification of the genetic components of disease risks, many of which have not been unveiled before and have opened a new avenue to understanding disease, treatment, and prevention.This chapter presents an overview of GWA, an important tool for discovering regions of the genome that harbor common genetic variants to confer susceptibility for various diseases or health outcomes in the post-Human Genome Project era. A tutorial on how to conduct a GWA study and some practical challenges specifically related to the GWA design is presented, followed by a detailed GWA case study involving the identification of loci associated with glioma as an example and an illustration of current technologies.